Interstitial Washdown and Vascular Albumin Refill During Fluid Infusion: Novel Kinetic Analysis From Three Clinical Trials

Abstract

Background and Aims. Increased capillary filtration may paradoxically accelerate vascular refill of both fluid and albumin from the interstitial space, which are claimed to be edema-preventing. We characterized “interstitial washdown” by kinetic analyses of the hemodilution induced by intravenous infusion of crystalloid fluid during 3 distinctphysiological states.Methods. The dilution of blood hemoglobin and plasma albumin was compared by population volume kinetic analysis during and after intravenous infusion Ringer´s solution over 30 min in 24 conscious volunteers and 30 anesthetized patients. Data were also retrieved from 31 patients with ketoacidosis from hyperglycemia who received 1 L of0.9% saline. Greater plasma dilution of hemoglobin as compared to albumin indicated recruitment of albumin.Results. “Interstitial washdown” increased plasma albumin concentration by 0.6 g/L in volunteers, by 1.0 g/L during anesthesia, and by 0.3 g/L in ketoacidosis patients. The albumin concentration in extravascular fluid returning to the plasma was approximately 29, 29, and 22 g/L during the respective infusions, but decreased to an average of 50% to 75% lower during the subsequent 2-3 h. Pronounced washdown was associated with increased capillary filtration (high k12) and, in conscious subjects, with fluid retention due to restricted urine flow. During anesthesia, the main effect was an increase the nonexchangeable fluid volume (“third-spacing”).Conclusions. Fluid infusion induces interstitial washdown by accelerated lymphatic flow and an increase in plasma albumin. The mechanism becomes exhausted after 2-3 hours. Albumin refill helps retain infused volume within the vascular compartment.

Albumin Kinetics in Sepsis and COVID-19

“…Compared with survivors, age of the population (78 vs 64 yr), underlying severity of illness (Sequential Organ Failure Assessment score: 12 vs 9), comorbidities like active hematological cancer (17% vs 6.8%) and liver disease (29% vs 14%), prevalence of pneumonia (56% vs 38%), and intra-abdominal sepsis (25% vs 18%) were significantly higher in the nonsurvivors. Thus, plausible mechanisms behind the observed albumin trends in nonsurvivors could be high protein nutrition therapy, enhanced hepatic albumin synthesis (acute phase response), and resuscitative measures like hyperoncotic albumin infusions, blood products, or fluid resuscitation leading to PA enrichment by interstitial washdown and enhanced vascular refill of albumin by lymphatics (7). Additionally, host response in sepsis is heterogeneous involving a complex interplay between pro-and anti-inflammatory pathways and may not have a uniform albumin kinetics.…”